This paper describes research into modelling, estimation and control of fed batch fermentation and an application to a large fermentation plant producing secondary metabolites. The problems are examined in a general sense from the viewpoints of both biological science and control engineering. Very extensive modelling and estimation work has been carried out. Only the most significant outcomes are reported here but references to the detailed research are given. Some of the research has resulted in the development of a novel advanced supervisory system- the Intelligent Process Management System (IPMS). Experience of applying the IPMS to a large-scale production process is described. The software has been designed on a modular basis and although implemented initially at one production plant, the approach is generic and fundamentally plant-independent so that further application to a range of other plants is envisaged.
Aborhey, S., and Williamson, D.1978. 'State and parameter estimation of microbial growth processes' , Automatica, 14, 493-498.
2.
Bastin, G., Dochain, D., Haest, M., Installe, M., and Opdenacker, P.1982. 'Modelling and adaptive control of a continuous anaerobic fermentation process', IFAC Modelling and Control of Biotechnical Processes, Helsinki, Finland, 299-306.
3.
Behal, V.1987. 'The tetracycline fermentation and its regulation' , CRC Critical Reviews in Biotechnology, 5(4), 275-318.
4.
Cazzador, L.1988. 'On the optimal control of fed-batch reactors with substrate-inhibited kinetics', Biotech Bioeng, 31, 670-674.
5.
Dahhou, B., Chamilothoris, G., and Roux, G.1991a. 'Adaptive predictive control of a continuous fermentation process, Int J Adapt Cont Sig Proc, 5,351-362.
6.
Dahhou, B., Roux, G., Queinnec, I., and Pourciel, J.B.1991b. 'Adaptive pole placement control of a continuous fermentation process', Int J SystemsSci, 22(12), 2625-2638.
7.
Dekkers, R.M.1982. 'State estimation of a fed-batch baker's yeast fermentation' , IFAC Modelling and Control of Biotechnical Processes, Helsinki, Finland, 201-211.
8.
Demain, A.L.1992. 'Microbial secondary metabolism: a new theoretical frontier for academia, a new opportunity for industry'. In: Secondary Mentabolites their Function and Evolution, Wiley , Chichester, (Ciba Foundation Symposium 171), 3-23.
9.
Dochain, D., and Bastin, G.1985. 'Stable adaptive algorithms for estimation and control of fermentation processes'. In: A Johnson (Ed), IFAC Modelling and Control of Biotechnological Processes , Noordwijkerhout, 37-42.
10.
Espeso, E.A., Tiburn, H. N.Arst Jr , and Penalva, M.A.1993. 'pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene', EMBO Journal, 12(10), 3947-3956.
11.
Flaus, J.M., Cheruy, A., Engasser, J.M., Poch, M., and Sola, C.1991. 'Estimation of the state and parameters in bioprocesses from indirect measurement', ECC91 European Control Conference, Grenoble, France, Vol 2, 1632-1647,
12.
Ghoul, M., Pons, M.-N., Engasser, J.-M., and Bordet, J.1985. 'Extended Kalman filtering technique for the on-line control of Candida utilis production'. In: A Johnson (Ed), IFAC Modelling and Control of Biotechnological Processes , Noordwijkerhout, 185-189.
13.
Goodacre, R., Trew, S., Wrigley-Jones, C., Neal, M.J., Maddock, J., Outley, T.W., Porter, N., and Kell, D.B.1994. 'Rapid screening for metabolite overproduction using pyrolysis mass spectrometry with multivariate calibration and artificial neural networks ', Biotechnol Bioeng, 44, 1205-1216.
14.
Goodacre, R., Trew, S., Wrigley-Jones, C., Saunders, G., Neal, M.J., Porter, N., and Kell, D.1995. 'Rapid and quantitative analysis of metabolites in fermentor broths using pyrolysis mass spectrometry with supervised learning: application to the screening of Penicillium chrysogenum fermentations for the overproduction of penicillins', Analytica Chima Acta, 313, 25-43.
15.
Hamer, J.W., and Richenberg, C.B.1988. 'On-line optimizing control of a packed-bed immobilized-cell reactor', AIChEJ, 34(4), 626-632.
16.
Heijden, R.T.J.M.V.D., Hellinga, C., Luyben, K.C.A.M., and Honderd, G.1989. 'State estimators (observers) for the on-line estimation of non-measurable process variables', TIBTECH, 7, 205-209.
17.
Henson, M.A., and Seborg, D.E.1992. 'Nonlinear control strategies for continuous fermenters', Chem EngSci, 47(4), 821-835.
18.
Hidalgo, E., and Demple, B.1994. 'An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein'. EMBO Journal , 13(1), 138-146.
19.
Hilaly, A.K., Karim, M.N., and Guyre, D.1994. 'Optimization of an industrial microalgae fermentation' , Biotech Bioeng, 43(4), 314-320.
20.
Hitzmann, B., Schongarth, K., Lohn, A., and Weigel, B.1995. 'Projective reference evaluation - The reliable evaluation technique for flow injection analysis signals'. In: A. Munack and K. Schugert (Eds), 6th International Conference on Computer Application in Biotechnology . Garmisch-Partenkirchen, Germany: Elsevier, 17-23.
21.
Hong, J.1986. 'Optimal substrate feeding policy for a fed batch fermentation with substrate and product inhibition kinetics', Biotech Bioeng , 28, 1421-1431.
22.
Hoo, K.A., and Kantor, J.C.1986. 'Global linearization and control of a mixed-culture bioreactor with competition and external inhibition', Math Biosci, 82,43-62.
23.
Jalel, N.A., Tsaptsinos, D., and Leigh, J.R.1993. 'Neural Networks for Modelling and Control of the Fed-Batch Fermentation Process', 3rd IEE International Conference on Artificial Neural Networks, Brighton, 25-27 May.
24.
Johnson, A.1987. 'The control of fed batch fermentation process - A survey' , Automatica, 23(6), 691-705.
25.
Kaiser, H., and Burns, J.A.1973. 'The control of flux. In: D. D. Davies (Ed), Rate control of biological processes, Symposium of the Society for Experimental Biology, Cambridge University Press, 27, 65-104.
26.
Kell, D. B., Van Dam, K., and Westerhoff, H. V. 1989. 'Growth analysis of microbial growth and productivity'. In: S. Baumberg, I. S. Hunter and P. M. Rhodes (Eds) Microbial products: new approaches, Symposium of the Society of General Microbiology, Cambridge University Press, 44, 61-93.
27.
Leigh, J. R. (Ed). 1986. Modelling and Control of Fermentation Processes, PeterPeregrinus .
28.
Lim, H.C., Tayeb, Y.J., Modak, J.M., and Bonte, P.1986. 'Computational algorithms for optimal feed rates for a class of fed-batch fermentation: numerical results far penicillin and cell mass production', Biotech Bioeng, 28, 1408-1420.
29.
Linko, P., and Zhu, Y.H.1992. 'Neural network modelling for real-time variable estimation and prediction in the control of glucoamylase fermentation', ProcBiochem, 27, 275-286.
30.
Melin, C., Laanait, A., Delarue, F., and Cordonnier, M.1982. 'Direction digital control and adaptive control algorithms for a pilot scale fermentor: some applications', IFAC Modelling and Control of Biotechnical Processes, Helsinki, Finland, 283-289.
31.
Mirzai, A.R., Leigh, J.R., Hou, Y.C., and Keshavarz, T.1990. 'Application of Kalman filter estimators to a fed-batch fermentation process'. In: E. Arikan (Ed), Communication, Control and Signal Processing, Elsevier Science Publishers BV. 1718,-1724.
32.
Modak, J.M., and Lim, H.C.1987. 'Feedback optimization of fed-batch fermentation' , Biotech Bioeng, 30, 528-540.
33.
Montague, G.A., Morris, A.J., and Tham, M.T.1992. 'Enhancing bioprocess operability with generic software sensors', J Biotech, 25, 183-201.
34.
Montague, G.A., Morris, A.J., Wright, A.R., Aynsley, M., and Ward, A.1985. 'Parameter adaptive control of the fed-batch penicillin fermentation. In: A Johnson (Ed), IFAC Modelling and Control of Biotechnological Processes, Noordwijkerhout, 69-74.
35.
Nahlik, J., and Burianec, Z.1988. 'On-line parameter and state estimation of continuous cultivation by extended Kalman filter', Appl Microbiol Biotechnol , 28, 128-134.
36.
Proll, T., and Karim, N.M.1994. "Nonlinear control of a bioreactor model using exact and I/O linearization', Int J Control, 60(4). 599-519.
37.
Ramirez, W.F.1987. 'Optimal state and parameter identification: an application to batch fermentation', Chem EngSci, 42(11), 2749-2756.
38.
Ramseier, M., Agrawal, P., and Mellichamp, D.A.1992. 'Non-linear adaptive control of fermentation processes utilizing a priori modelling knowledge', J Proc Cont, 2(3), 129-138.
39.
Roux, G., Dahhou, B., Najim, K., and Queinnec, I.1992. 'Adaptive linear quadratic guassian (LQG) control of a bioreactor', J Chem Tech Biotechnol, 53, 133-141.
40.
Samaan, M., Dahhou, T., Queinnec, I., and Msaad, M.1990. 'Experimental results in adaptive control of biotechnological processes', American Control Conferences, San Diego, California, 2679-2683.
41.
Saucedo, V.M., Valentinotti, S.C., Karim, M.N., and Collins, H.W.1995. 'Feedback control of a recombinant fed-batch fermentation using on-line HPLC measurements'. In: A Munack and K. Schugerl (Eds), 6th International Conference on Computer Application in Biotechnology. Garmisch-Partenkirchen, Germany: Elsevier, 24-28.
42.
Semones, G.B., and Lim, H.C.1989. 'Experimental multivariable adaptive optimisation of the steady-state cellular productivity of a continuous baker's yeast culture' , Biotech Bioeng, 33, 16-25.
43.
Shimizu, H., Araki, K., Shioya, S., and Suga, K-I.1991. 'Optimal production of glutathione by controlling the specific growth rate of yeast in fed-batch culture', Biotech Bioeng, 38, 196-205.
44.
Stephanopoulos, G., and San, K-Y.1984. 'Studies on on-line bioreactor identification 1. theory ', Biotech Bioeng, 26, 1176-1188.
45.
Stortz, G., Tartaglia, L.A., and Ames, B.N.1990. 'Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation', Science, 248, 189-194.
46.
Thatipamala, R., Hill, G.A., and Rohani, S.1993. 'On-line state and parameter estimation and adaptive optimization of a continuous bioreactor (ethanol fermentation) using state equations', American Control Conference 1994, San Francisco, California. Vol 1,905-909.
47.
Tsao, J-H., Chuang, H-L., and Wu, W-T.1991. 'On-line state estimation and control in glutamic acid production', Bioprocess Eng, 7, 35-39.
48.
Tsaptsinos, D., and Leigh, J.R.1993. Modelling of a fermentation process using multi-layered perceptrons', JMicrocomputer Applications, 16, 125-136.
49.
Tsaptsinos, D., Jalel, N.A., and Leigh, J.R.1992. 'Estimation of state variables of a fermentation process via Kalman filter and neural network', Colloq University of Liverpool, 11 March.
50.
Vanichsriratana, W., McFarlane, D., Keshavarz, T., and Leigh, J.R.1996. 'Comparison of open loop optimal control and closed loop optimal control of a fermentation process', Proc IEE International Control Conference96, Exeter , UK, 244-247.
51.
Vanichsriratana, W., Zhang, B.S., and Leigh, J.R.1997. 'Optimal control caf a fed-batch fermentation process' , Trans Inst Measure and Control, 19(5), 240-251.
52.
Vigie, P., Dohhou, B., Queinnec, I., Lakrori, M., Cheruy, A., and Pourciel, J.B.1991. 'Control of substrate concentration in a continuous bioprocess' , Bioprocess Engineering, 6, 259-263.
53.
Williams, D., and Montgomery, P.A.1986. 'Multivariable adaptive control of baker's yeast fermentation', IEE Proc-D, 133(5), 247-253.
54.
Williams, D., Yousefpour, P., and Swanick, B.H.1984. "On-line adaptive control of a fermentation process' , IEE Proc-D, 131(4), 117-124.
55.
Zhang, B.S., and Leigh, J.R. (in preparation). 'Design of optimal state estimator for a special class of problems'.
56.
Zhang, B.S., and Leigh, J.R.1993. 'Predictive time-sequence iterative learning control with applications to a fermentation process', Proc 2nd IEEE Conf on Control Applications, September 13-16, Vancouver , Canada, Vol 1, 439—442.
57.
Zhang, B.S., Tang, R., and Leigh, J.R.1995. "Modelling and control of a fed-batch fermentation process using neural networks and iterative learning methods'. In: A. Munack and K. Schugerl (Eds), 6th International Conference on Computer Application in Biotechnology, Garmisch-Partenkirchen, Germany: Elsevier , 101-106.
58.
Zhang; B.S., Tang, R., Leigh, J.R., Dixon, K., and Hinge, R.D.1996. 'Improved quality and productivity is secondary metabolite fermentation through estimation control and scheduling', 13th IFAC World Congress, San Francisco , June 30-July 5.
